The use of L-ascorbic acid as an anti-oxidant in food preparations is known. For example, Steinhart, Pro- and Antioxidative Effect of Ascorbic Acid on L-Tryptophan in the System Fe.sup.3 +/Ascorbic Acid/O.sub.2, J. Agric. Food Chem., Vol. 41, pages 2275-2277 (1993) describes the use of L-ascorbic acid as an anti-oxidant which performs its function in food by removing free radicals and undergoing rapid oxidation itself.
Similarly, free L-ascorbic acid in topical preparations demonstrates poor stability and tends to break down due to partially oxidative and non-oxidative degradation. The degraded ascorbic acid loses activity and the host product loses aesthetic appeal by exhibiting a brown color which is unacceptable for commercial cosmetics.
Although cholesterol, especially in the ingested form, is considered unhealthy, the benefits of cholesterol unassociated with L-ascorbic acid for skin barrier repair are known. For example, Menon, Structural Basis for the Barrier Abnormality Following Inhibition of HMG CoA Reductase in Murine Epidermis, J. Invest. Dermatol., Vol. 98, pages 209-219 (1992), describes deficiencies noted in the skin barrier repair mechanism when cholesterol synthesis is inhibited by down-regulation of HMG CoA reductase.
Mechanical mixing of L-ascorbic acid and cholesterol according to currently available methods results in a product which is also unstable due to the over-riding problem of L-ascorbic acid instability. For example, U.S. Pat. No. 4,939,128, at column 3, lines 21-22, describes ascorbic acid in conjunction with a cholestanyl group. The conspicuous absence of cholesterol and the specific mention of a cholestanyl group reflects a recognition, prior to the present disclosure, that conjugates of L-ascorbic acid and cholesterol were not practical or desired.
Attempts have also been made to conjugate ascorbic acid with a glycyrrhetic group as described in European Application No. 92104149.7; and with a tocopheryl group as indicated by U.S. Pat. No. 3,151,127. U.S. Pat. Nos. 4,564,686 and 5,306,713 also disclose tocopheryl ascorbyl phosphate as an anti-oxidant having the following structure. ##STR2##
Sakamoto, Measurement Method of Efficacy of Antidandruff Cosmetics and Development of the New Active Commercial Product, IFSCC, Yokohama, Vol. B206, pages 823-864 (1993) describes the use of tocopheryl coupled to L-ascorbic acid. The coupled tocopheryl is an anti-oxidant preservative for the ascorbyl group, but the use of the ascorbyl-tocopheryl as a skin therapeutic is questionable because, unlike cholesterol, tocopheryl is not a natural substrate for the skin.
The art requires a method for covalently and bioreversibly coupling cholesterol to L-ascorbic acid. The coupled molecule should be stable so that full functional activity is retained even after decoupling by naturally occurring acidic phosphatases in the skin. The beneficial properties of L-ascorbic acid would be provided, including increased collagen production and skin-lightening, combined with the benefits of released cholesterol for improved elasticity, resistance, tone and moisture retention of the skin.